Studies of acute, latent and reactivated herpes simplex virus (HSV) infection of the peripheral autonomic nervous system will be continued because: 1) infection of autonomic ganglia with HSV in man may be of importance both in the production of disease and in the transmission of virus; 2) infection with HSV serves as a paradigm of viral infection of the autonomic nervous system, allowing exploration of possible pathogenetic mechanisms involved in neuronal and target organ dysfunction and disease; and 3) advanced knowledge and facility of experimental manipulation of the autonomic nervous system provide a valuable foundation for exploring the pathogenesis of HSV infection of the nervous system, particularly cellular determinants of whether infection is to be lytic, latent or reactivated. In vivo and in vitro models will provide 2 complementary approaches to achieve this end. Studies employing a murine model of in vivo latent infection of the superior cervical ganglion (SCG) of the sympathetic division of the autonomic nervous system will continue in efforts to define factors which modulate the permissiveness of ganglion cells in vivo during the acute and latent phases of infection and also to characterize the cellular changes accompanying reactivation of latent virus as well as the ganglion and target organ sequelae of reactivation. Dissociated cell cultures derived from sympathetic ganglia will be used to further characterize productive infection of neural cells in vitro and to define factors which influence the permissiveness of these cells for HSV. These cultures will also be used to develop an in vitro model of latency which corresponds mechanistically to in vivo infection and can be used to investigate the stimuli and cellular changes associated with reactivation of HSV. These studies will allow insight into the cellular basis of the variability of HSV infection in man, provide systems for future biochemical characterization of latency and reactivation, and perhaps open new avenues of prevention and treatment of human disease caused by this virus.